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Protein

Type II inositol 1,4,5-trisphosphate 5-phosphatase

Gene

INPP5B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.1 Publication

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 4-phosphate + phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi355Magnesium1 Publication1
Metal bindingi383Magnesium1 Publication1
Binding sitei383Substrate1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS05898-MONOMER.
ZFISH:HS05898-MONOMER.
BRENDAi3.1.3.36. 2681.
ReactomeiR-HSA-1855183. Synthesis of IP2, IP, and Ins in the cytosol.
R-HSA-1855204. Synthesis of IP3 and IP4 in the cytosol.
R-HSA-194840. Rho GTPase cycle.
SABIO-RKP32019.

Names & Taxonomyi

Protein namesi
Recommended name:
Type II inositol 1,4,5-trisphosphate 5-phosphatase (EC:3.1.3.36)
Alternative name(s):
75 kDa inositol polyphosphate-5-phosphatase
Phosphoinositide 5-phosphatase
Short name:
5PTase
Gene namesi
Name:INPP5B
Synonyms:OCRL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6077. INPP5B.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi990C → S: Loss of prenylation and membrane localization. 1 Publication1

Organism-specific databases

DisGeNETi3633.
OpenTargetsiENSG00000204084.
PharmGKBiPA29885.

Polymorphism and mutation databases

BioMutaiINPP5B.
DMDMi281185510.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000156401 – 990Type II inositol 1,4,5-trisphosphate 5-phosphataseAdd BLAST990
PropeptideiPRO_0000422293991 – 993Removed in mature formSequence analysis3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei990Cysteine methyl esterSequence analysis1
Lipidationi990S-farnesyl cysteineSequence analysis1

Post-translational modificationi

Isoprenylation at Cys-990 may be required for localization at the membrane.1 Publication
May be proteolytically cleaved after Lys-320 as inferred from N-terminal protein sequence of the 75 kda form.1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Prenylation

Proteomic databases

EPDiP32019.
MaxQBiP32019.
PaxDbiP32019.
PeptideAtlasiP32019.
PRIDEiP32019.

PTM databases

DEPODiP32019.
iPTMnetiP32019.
PhosphoSitePlusiP32019.

Expressioni

Tissue specificityi

Platelets.

Gene expression databases

BgeeiENSG00000204084.
CleanExiHS_INPP5B.
ExpressionAtlasiP32019. baseline and differential.
GenevisibleiP32019. HS.

Organism-specific databases

HPAiHPA028803.

Interactioni

Subunit structurei

Interacts with APPL1, FAM109A and FAM109B. Interacts with several Rab GTPases, at least RAB1A, RAB2A, RAB5A, RAB6A, RAB8A, RAB9A and RAB33B; these interactions may play a dual role in targeting INPP5B to the specific membranes and stimulating the phosphatase activity. Interacts with INPP5F (PubMed:25869668).5 Publications

Protein-protein interaction databases

BioGridi109845. 20 interactors.
IntActiP32019. 17 interactors.
STRINGi9606.ENSP00000362115.

Structurei

Secondary structure

1993
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi340 – 353Combined sources14
Helixi364 – 367Combined sources4
Beta strandi368 – 370Combined sources3
Beta strandi375 – 382Combined sources8
Helixi388 – 391Combined sources4
Helixi397 – 409Combined sources13
Beta strandi416 – 424Combined sources9
Beta strandi427 – 434Combined sources8
Helixi435 – 440Combined sources6
Beta strandi441 – 450Combined sources10
Helixi453 – 455Combined sources3
Beta strandi460 – 469Combined sources10
Beta strandi472 – 480Combined sources9
Helixi485 – 487Combined sources3
Helixi488 – 501Combined sources14
Beta strandi509 – 511Combined sources3
Beta strandi518 – 527Combined sources10
Helixi537 – 545Combined sources9
Helixi549 – 553Combined sources5
Helixi557 – 563Combined sources7
Beta strandi566 – 568Combined sources3
Beta strandi588 – 591Combined sources4
Beta strandi594 – 596Combined sources3
Beta strandi604 – 620Combined sources17
Beta strandi626 – 629Combined sources4
Beta strandi632 – 643Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MTCX-ray2.40A339-643[»]
3N9VX-ray2.65A/B342-646[»]
4CMLX-ray2.30A339-643[»]
5A7IX-ray2.89A339-643[»]
5A7JX-ray2.90A/B339-643[»]
ProteinModelPortaliP32019.
SMRiP32019.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP32019.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 148PHAdd BLAST127
Domaini821 – 993Rho-GAPPROSITE-ProRule annotationAdd BLAST173

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni342 – 6685-phosphataseBy similarityAdd BLAST327
Regioni459 – 460Substrate binding2
Regioni582 – 583Substrate binding2
Regioni596 – 598Substrate binding3
Regioni669 – 782ASHBy similarityAdd BLAST114

Domaini

The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by FAM109A and FAM109B as endosomes mature, all three interactions relie on F&H motifs, an approximately 12-13 amino-acid sequence centered around Phe and His residues essential for binding (By similarity).By similarity

Sequence similaritiesi

Contains 1 PH domain.Curated
Contains 1 Rho-GAP domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
KOG4270. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00760000119075.
HOVERGENiHBG000070.
InParanoidiP32019.
KOiK01099.
OMAiHIEEYER.
OrthoDBiEOG091G02KE.
PhylomeDBiP32019.
TreeFamiTF317034.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR031896. INPP5B_PH_dom.
IPR000300. IPPc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
PF16776. INPP5B_PH. 1 hit.
PF00620. RhoGAP. 1 hit.
[Graphical view]
SMARTiSM00128. IPPc. 1 hit.
SM00324. RhoGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 2 hits.
SSF56219. SSF56219. 1 hit.
PROSITEiPS50238. RHOGAP. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P32019-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDQSVAIQET LAEGEYCVIA VQGVLCEGDS RQSRLLGLVR YRLEHGGQEH
60 70 80 90 100
ALFLYTHRRM AITGDDVSLD QIVPVSRDFT LEEVSPDGEL YILGSDVTVQ
110 120 130 140 150
LDTAELSLVF QLPFGSQTRM FLHEVARACP GFDSATRDPE FLWLSRYRCA
160 170 180 190 200
ELELEMPTPR GCNSALVTWP GYATIGGGRY PSRKKRWGLE EARPQGAGSV
210 220 230 240 250
LFWGGAMEKT GFRLMERAHG GGFVWGRSAR DGRRDEELEE AGREMSAAAG
260 270 280 290 300
SRERNTAGGS NFDGLRPNGK GVPMDQSSRG QDKPESLQPR QNKSKSEITD
310 320 330 340 350
MVRSSTITVS DKAHILSMQK FGLRDTIVKS HLLQKEEDYT YIQNFRFFAG
360 370 380 390 400
TYNVNGQSPK ECLRLWLSNG IQAPDVYCVG FQELDLSKEA FFFHDTPKEE
410 420 430 440 450
EWFKAVSEGL HPDAKYAKVK LIRLVGIMLL LYVKQEHAAY ISEVEAETVG
460 470 480 490 500
TGIMGRMGNK GGVAIRFQFH NTSICVVNSH LAAHIEEYER RNQDYKDICS
510 520 530 540 550
RMQFCQPDPS LPPLTISNHD VILWLGDLNY RIEELDVEKV KKLIEEKDFQ
560 570 580 590 600
MLYAYDQLKI QVAAKTVFEG FTEGELTFQP TYKYDTGSDD WDTSEKCRAP
610 620 630 640 650
AWCDRILWKG KNITQLSYQS HMALKTSDHK PVSSVFDIGV RVVNDELYRK
660 670 680 690 700
TLEEIVRSLD KMENANIPSV SLSKREFCFQ NVKYMQLKVE SFTIHNGQVP
710 720 730 740 750
CHFEFINKPD EESYCKQWLN ANPSRGFLLP DSDVEIDLEL FVNKMTATKL
760 770 780 790 800
NSGEDKIEDI LVLHLDRGKD YFLSVSGNYL PSCFGSPIHT LCYMREPILD
810 820 830 840 850
LPLETISELT LMPVWTGDDG SQLDSPMEIP KELWMMVDYL YRNAVQQEDL
860 870 880 890 900
FQQPGLRSEF EHIRDCLDTG MIDNLSASNH SVAEALLLFL ESLPEPVICY
910 920 930 940 950
STYHNCLECS GNYTASKQVI STLPIFHKNV FHYLMAFLRE LLKNSAKNHL
960 970 980 990
DENILASIFG SLLLRNPAGH QKLDMTEKKK AQEFIHQFLC NPL
Note: No experimental confirmation available.
Length:993
Mass (Da):112,852
Last modified:December 15, 2009 - v4
Checksum:iABD3581CC6CD29D6
GO
Isoform 2 (identifier: P32019-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     178-257: Missing.

Show »
Length:913
Mass (Da):103,987
Checksum:i4882C26F6E4DC9C6
GO
Isoform 3 (identifier: P32019-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-244: Missing.

Show »
Length:749
Mass (Da):85,620
Checksum:i50921FAACF7E1E39
GO
Isoform 4 (identifier: P32019-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     810-828: TLMPVWTGDDGSQLDSPME → LAYLAAYCFETQLVTKSLI
     829-993: Missing.

Note: No experimental confirmation available.
Show »
Length:828
Mass (Da):93,924
Checksum:i9CD5C12DCF509A50
GO

Sequence cautioni

The sequence AAA79207 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti587 – 606GSDDW…WCDRI → RALTTGIPVRSAVLLPGVIG F AA sequence (PubMed:1718960).CuratedAdd BLAST20
Sequence conflicti911G → P AA sequence (PubMed:1718960).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06127046G → S.Corresponds to variant rs56993041dbSNPEnsembl.1
Natural variantiVAR_028002745M → T.3 PublicationsCorresponds to variant rs11488569dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0128211 – 244Missing in isoform 3. CuratedAdd BLAST244
Alternative sequenceiVSP_012820178 – 257Missing in isoform 2. 1 PublicationAdd BLAST80
Alternative sequenceiVSP_013902810 – 828TLMPV…DSPME → LAYLAAYCFETQLVTKSLI in isoform 4. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_013903829 – 993Missing in isoform 4. 1 PublicationAdd BLAST165

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M74161 mRNA. Translation: AAA79207.1. Different initiation.
AL603790, AL929472 Genomic DNA. Translation: CAH69926.1.
AL603790, AL929472 Genomic DNA. Translation: CAH69928.1.
AL603790, AL929472 Genomic DNA. Translation: CAH69929.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70076.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70079.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70080.1.
BX296560 Genomic DNA. No translation available.
BC042529 mRNA. Translation: AAH42529.2.
BC058932 mRNA. Translation: AAH58932.1.
AL833055 mRNA. Translation: CAH56301.1.
CCDSiCCDS41306.1. [P32019-2]
CCDS72760.1. [P32019-3]
RefSeqiNP_001284363.1. NM_001297434.1. [P32019-3]
NP_005531.2. NM_005540.2. [P32019-2]
UniGeneiHs.449942.

Genome annotation databases

EnsembliENST00000373023; ENSP00000362114; ENSG00000204084. [P32019-1]
ENST00000373024; ENSP00000362115; ENSG00000204084. [P32019-2]
ENST00000373026; ENSP00000362117; ENSG00000204084. [P32019-1]
ENST00000373027; ENSP00000362118; ENSG00000204084. [P32019-3]
GeneIDi3633.
KEGGihsa:3633.
UCSCiuc001ccf.1. human. [P32019-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M74161 mRNA. Translation: AAA79207.1. Different initiation.
AL603790, AL929472 Genomic DNA. Translation: CAH69926.1.
AL603790, AL929472 Genomic DNA. Translation: CAH69928.1.
AL603790, AL929472 Genomic DNA. Translation: CAH69929.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70076.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70079.1.
AL929472, AL603790 Genomic DNA. Translation: CAH70080.1.
BX296560 Genomic DNA. No translation available.
BC042529 mRNA. Translation: AAH42529.2.
BC058932 mRNA. Translation: AAH58932.1.
AL833055 mRNA. Translation: CAH56301.1.
CCDSiCCDS41306.1. [P32019-2]
CCDS72760.1. [P32019-3]
RefSeqiNP_001284363.1. NM_001297434.1. [P32019-3]
NP_005531.2. NM_005540.2. [P32019-2]
UniGeneiHs.449942.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MTCX-ray2.40A339-643[»]
3N9VX-ray2.65A/B342-646[»]
4CMLX-ray2.30A339-643[»]
5A7IX-ray2.89A339-643[»]
5A7JX-ray2.90A/B339-643[»]
ProteinModelPortaliP32019.
SMRiP32019.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109845. 20 interactors.
IntActiP32019. 17 interactors.
STRINGi9606.ENSP00000362115.

PTM databases

DEPODiP32019.
iPTMnetiP32019.
PhosphoSitePlusiP32019.

Polymorphism and mutation databases

BioMutaiINPP5B.
DMDMi281185510.

Proteomic databases

EPDiP32019.
MaxQBiP32019.
PaxDbiP32019.
PeptideAtlasiP32019.
PRIDEiP32019.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373023; ENSP00000362114; ENSG00000204084. [P32019-1]
ENST00000373024; ENSP00000362115; ENSG00000204084. [P32019-2]
ENST00000373026; ENSP00000362117; ENSG00000204084. [P32019-1]
ENST00000373027; ENSP00000362118; ENSG00000204084. [P32019-3]
GeneIDi3633.
KEGGihsa:3633.
UCSCiuc001ccf.1. human. [P32019-1]

Organism-specific databases

CTDi3633.
DisGeNETi3633.
GeneCardsiINPP5B.
HGNCiHGNC:6077. INPP5B.
HPAiHPA028803.
MIMi147264. gene.
neXtProtiNX_P32019.
OpenTargetsiENSG00000204084.
PharmGKBiPA29885.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0565. Eukaryota.
KOG4270. Eukaryota.
COG5411. LUCA.
GeneTreeiENSGT00760000119075.
HOVERGENiHBG000070.
InParanoidiP32019.
KOiK01099.
OMAiHIEEYER.
OrthoDBiEOG091G02KE.
PhylomeDBiP32019.
TreeFamiTF317034.

Enzyme and pathway databases

BioCyciMetaCyc:HS05898-MONOMER.
ZFISH:HS05898-MONOMER.
BRENDAi3.1.3.36. 2681.
ReactomeiR-HSA-1855183. Synthesis of IP2, IP, and Ins in the cytosol.
R-HSA-1855204. Synthesis of IP3 and IP4 in the cytosol.
R-HSA-194840. Rho GTPase cycle.
SABIO-RKP32019.

Miscellaneous databases

ChiTaRSiINPP5B. human.
EvolutionaryTraceiP32019.
GeneWikiiINPP5B.
GenomeRNAii3633.
PROiP32019.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204084.
CleanExiHS_INPP5B.
ExpressionAtlasiP32019. baseline and differential.
GenevisibleiP32019. HS.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR031896. INPP5B_PH_dom.
IPR000300. IPPc.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
PF16776. INPP5B_PH. 1 hit.
PF00620. RhoGAP. 1 hit.
[Graphical view]
SMARTiSM00128. IPPc. 1 hit.
SM00324. RhoGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 2 hits.
SSF56219. SSF56219. 1 hit.
PROSITEiPS50238. RHOGAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiI5P2_HUMAN
AccessioniPrimary (citable) accession number: P32019
Secondary accession number(s): C9J6U5
, Q5VSG9, Q5VSH0, Q5VSH1, Q658Q5, Q6P6D4, Q6PD53, Q86YE1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: December 15, 2009
Last modified: November 30, 2016
This is version 157 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.